Therapeutic Hypothermia Does Not Mitigate Iron-Induced Injury in Rat

Abstract

Intracerebral hemorrhage (ICH) is often a devastating stroke, and there are no clinically proven neuroprotective treatments. Considerable research points to iron toxicity as a leading contributor to secondary damage after ICH. Iron, released from degraded erythrocytes, catalyzes free radical production, thereby causing cell death in the ensuing days and weeks. Therapeutic hypothermia (TH) is a potential neuroprotective strategy for ICH, but results from animal studies are inconsistent and generally weaker than that found in ischemia models. Thus, we examined whether TH (∼33°C for 24–72 hours) would specifically mitigate iron toxicity, which we modeled by infusing 3.8 μg of FeCl₂ in 30 μL of sterile saline into the striatum of rats. Rats were subjected to whole-body cooling beginning 1 hour after FeCl₂ infusion. Use of TH reduced (p = 0.025) the small bleed caused by FeCl₂ infusion (∼6 μL). However, TH did not lessen FeCl₂-induced edema at 24 and 72 hours postinfusion, nor were behavioral impairments (e.g., walking) or brain injury (at 7 and 28 days) attenuated by TH. These results suggest that TH does not directly protect against iron toxicity, which indicates that this is not a means by which TH improves the outlook after ICH.